Tri-Mix Information

Intracavernosal Injection
According to the American Urologic Association, Intracavernous injections are the most effective non-surgical treatment for erectile dysfunction. Unlike oral medication, injection to the penis triggers an automatic and almost immediate erection. The individual can inject himself as little as five minutes prior to sexual activity and the effect should last for not more than an hour. Injections are used as a second line agent if oral therapy fails. Tri-mix compounds that are injected include phentolamine, papaverine and alprostadil. Increased efficacy and decreased side effects for some men may be seen with only alprostadil and phentolamine. These are combination therapies that include Tri-Mix and Bi-Mix. Both of these products must be compounded by specialty pharmacies and are not commercially available. Below is a general description of medications contained in Tri-mix and Bi-mix including their mechanisms of action, dose and side effects of each medication.Back to Top

Alprostodil
• Available as brand names Caverject® and Edex® commercially.
• Stimulates relaxation of smooth muscle and dilates the arteries in the penis to increase blood flow by increasing Prostaglandin E.
• About 75% of males show efficacy when injected in the penis.
• A starting dose of 10-15 mcg is given to patients who have failed previous oral therapy.
• A dose of 2.5-5 mcg is given to patients who have neurogenic or psychogenic erectile dysfunction and have either failed or refused oral therapy.
• An intermediate dose of 12-15 mcg is frequently used. No benefits are seen once the dose exceeds 40mcg. It is recommended to try a combination that includes papaverine, phentolamine or both.Side effects:
• Bruising - can be minimized by using proper injection technique and using a 30G needle.
• Fibrosis - Long term use of injection therapy can cause scarring of penile tissue. Scarring is reported to be lower with alprostadil than with other medications.
• Hypotension - although rare with alprostadil, can occur when drug is leaked out into the general circulation from the injected area.
• Liver function tests - can be occasionally increased.
• Penile pain - occurs in about 31% of patients during or after injection. It could be reduced if mixed with other agents.
• Priapism - If patient experiences prolonged erection lasting more than 4 hours, they should seek medical attention.Back to Top

Phentolamine
• Available as Brand name Regitine®
• Mechanism of action - It increases the blood flow to the penis by producing direct vasodilatation as it is an alpha-adrenergic antagonist.
• Usual recommended dose is 1-2 mg.Side effects:
• Priapism: If patient experiences prolonged erection lasting more than 4 hours, they should seek medical attention.
• Fibrosis: Long term use of injection therapy can cause scarring of penile tissue.
• Systemic hypotension (low blood pressure) : Hypotension, can occur when drug is leaked out into the general circulation from the injected area.
• Increase in heart rate also known as reflex tachycardia can occur.
• Nasal congestion
• Gastrointestinal upsetBack to Top

Papaverine
• Papaverine is not available commercially and must be used in combination with phentolamine in order to produce hard erections.
• Mechanism of action: Papaverine is a Phosphodiesterase inhibitor. Inhibition of Phosphodiesterase results in smooth muscle relaxation which allows increased blood flow to the penis.
• Mainly used in combination with alprostadil and/or phentolamine.
• It has been used for ED since the 1980’s but has not being approved for ED.
The usual dose for papavarine is 5 to 30mg.Side effects:
• Priapism: If patient experiences prolonged erection lasting more than 4 hours, they should seek medical attention.
• Fibrosis: Long term use of injection therapy can cause scarring of penile tissue.
• Systemic hypotension (low blood pressure): Hypotension, can occur when drug has leaked out into the general circulation from the injected areaBack to Top

Combination TherapyBi-Mix combination
• Bi-Mix is a combination of Papaverine and Phentolamine. It was first introduced in 1985 when a study showed a success rate of 71% in 250 patients. The patients received 1mg of phentolamine with 30mg of papaverine.
• Two more studies were published in 1987. One of the studies showed mixing papaverine with phentolamine had a success rate of 72.9% compared to using papaverine alone with success rate of only 20%.
• One of the studies followed up patients using the Bi-Mix combination for 26 months and only 13% of the patients failed to respond to the therapy.
• The usual prescribed strength of Bi-Mix is Papverine 6-25mg along with Phentolamine 0.05-2 mg/ml

Tri-Mix combination
• Tri-Mix is a combination of Papaverine, Phentolamine and, Alprostadil. This combination was first introduced by Bennett and his colleagues in 1991. The study demonstrated a success rate of 92% in 116 patients.
• To achieve maximum efficacy, lower pain incidence and decrease cost per dose; Tri-Mix is compounded using papaverine, phentolamine and alprostadil in one vial.
• Additional studies have been done that have shown that there is good efficacy in combination of all these medications in one formulation. Tri-Mix is reserved for patients who have failed either alprostadil, Bi-mix combination or those who have severe pain while using prostaglandin E1. The advantage of using Tri-Mix is that it uses lower doses of alprostadil and thus penile pain often subsides with Tri-Mix.
• The usual prescribed strength of Quad-Mix is Papaverine 20-25mg, Phentolamine 1.5-2.0mg, Prostaglandin E1 20-25mcg, and, atropine 0.02-0.08mg/ml.

Quad-Mix: Papaverine, Phentolamine, Alprostadil, Atropine
• Quad mix is a combination of alprostadil, atropine, papaverine and phentolamine. The atropine in the Quad-Mix causes smooth muscle relaxation in the penis and works synergistically with the other components. Israilov and colleagues conducted a study in which 13 patients who had failed tri-mix showed positive response to quad-mix. 53.8% (Seven) of the patients responded successfully with atropine addition.
• The usual prescribed strength of Quad-Mix is Papaverine 20-25mg, Phentolamine 1.5-2.0mg, Prostaglandin E1 20-25mcg, and, atropine 0.02-0.08mg/ml.

The information on this website should not be used to diagnose or treat patients without the specific direction and supervision of a physician. You should consult with a physician who knows your medical history and current medical conditions before using Tri-Mix or any erectile dysfunction treatments. Your treatment should be individualized for you by a prescribing physician. Tri-Mix is for the treatment of Erectile Dysfunction and is not approved by the FDA. Tri-Mix requires a prescription and can only be filled at a compounding pharmacy.
Copyright 2011